Sulfate conjugates are metabolite markers of inhalation exposure to 4-chlorobiphenyl (PCB3)

Abstract

Semi-volatile lower chlorinated PCBs (LC-PCBs), comprised of mostly tetra or lower chlorinated congeners, are detected in old buildings and outdoors in high concentrations. PCBs cause endocrine disruption, neurotoxicity and many other adverse effects, and are human carcinogens. Epidemiological studies so far have relied upon serum concentrations of PCBs or OH-PCBs as markers of exposure. Despite the detection of LC-PCBs in high levels in buildings and other environments, only a few studies have reported LC-PCBs in human serum. One of the reasons for low serum detection of LCPCBs could be the further biotransformation and excretion of OH-PCBs from the body. Therefore, the objective of this dissertation research was to study the metabolism of one of the LC-PCBs in rats and to identify a suitable metabolite marker of inhalation exposure for a future epidemiological study in humans. We chose PCB3 (4chlorobiphenyl), a mono chlorinated PCB found in high concentrations in many buildings, as a model to study the metabolism. The first aim was to identify final metabolites of PCB3 in vivo. Male SpragueDawley rats were held in metabolism cages following exposure to PCB3 via i.p. injection. Blood, urine and feces were collected, and an analytical method for extraction of PCB3 metabolites was developed. By identifying the metabolites by LC/MS, a complete biotransformation pathway for PCB3 was elucidated. Major urinary metabolites of PCB3 were sulfates and mercapturates, while glucuronides and free phenolic forms were minor. The second aim was to study the disposition and toxicity of phenolic and sulfate metabolites after inhalation exposure to PCB3 in female Sprague-Dawley rats. Airborne